title: Prenatal alcohol exposure and childhood atopic disease: a Mendelian randomization approach.
abstract: BACKGROUND
  Alcohol consumption in western pregnant women is not uncommon and could be a risk factor for childhood atopic disease. However, reported alcohol intake may be unreliable, and associations are likely to be confounded.
  
  
  OBJECTIVE
  We aimed to study the relation between prenatal alcohol exposure and atopic phenotypes in a large population-based birth cohort with the use of a Mendelian randomization approach to minimize bias and confounding.
  
  
  METHODS
  In white mothers and children in the Avon Longitudinal Study of Parents and Children (ALSPAC) we first analyzed associations between reported maternal alcohol consumption during pregnancy and atopic outcomes in the offspring measured at 7 years of age (asthma, wheezing, hay fever, eczema, atopy, and total IgE). We then analyzed the relation of maternal alcohol dehydrogenase (ADH)1B genotype (rs1229984) with these outcomes (the A allele is associated with faster metabolism and reduced alcohol consumption and, among drinkers, would be expected to reduce fetal exposure to ethanol).
  
  
  RESULTS
  After controlling for confounders, reported maternal drinking in late pregnancy was negatively associated with childhood asthma and hay fever (adjusted odds ratio [OR] per category increase in intake: 0.91 [95% CI, 0.82-1.01] and 0.87 [95% CI, 0.78-0.98], respectively). However, maternal ADH1B genotype was not associated with asthma comparing carriers of A allele with persons homozygous for G allele (OR, 0.98 [95% CI, 0.66-1.47]) or hay fever (OR, 1.11 [95% CI, 0.71-1.72]), nor with any other atopic outcome.
  
  
  CONCLUSIONS
  We have found no evidence to suggest that prenatal alcohol exposure increases the risk of asthma or atopy in childhood.
authors.affiliation: Centre for Primary Care and Public Health, Barts and The London School of Medicine and Dentistry, London, United Kingdom. Electronic address: s.shaheen@qmul.ac.uk.
authors.forename: Seif O
authors.initials: SO
authors.lastname: Shaheen
authors.affiliation: Centre for Primary Care and Public Health, Barts and The London School of Medicine and Dentistry, London, United Kingdom.
authors.forename: Clare
authors.initials: C
authors.lastname: Rutterford
authors.affiliation: School of Social and Community Medicine, University of Bristol, Bristol, United Kingdom; Medical Research Council Centre for Causal Analyses in Translational Epidemiology, University of Bristol, Bristol, United Kingdom.
authors.forename: Luisa
authors.initials: L
authors.lastname: Zuccolo
authors.affiliation: School of Social and Community Medicine, University of Bristol, Bristol, United Kingdom.
authors.forename: Susan M
authors.initials: SM
authors.lastname: Ring
authors.affiliation: School of Social and Community Medicine, University of Bristol, Bristol, United Kingdom; Medical Research Council Centre for Causal Analyses in Translational Epidemiology, University of Bristol, Bristol, United Kingdom.
authors.forename: George
authors.initials: G
authors.lastname: Davey Smith
authors.affiliation: Human Development and Health, Faculty of Medicine, University of Southampton, Southampton, United Kingdom.
authors.forename: John W
authors.initials: JW
authors.lastname: Holloway
authors.affiliation: School of Social and Community Medicine, University of Bristol, Bristol, United Kingdom.
authors.forename: A John
authors.initials: AJ
authors.lastname: Henderson
mesh_terms: D000328:Adult; D000426:Alcohol Dehydrogenase / Q000235:genetics*; D000428:Alcohol Drinking / Q000453:epidemiology* / Q000235:genetics; D001249:Asthma / Q000453:epidemiology* / Q000235:genetics; D002648:Child; D015331:Cohort Studies; D003876:Dermatitis, Atopic / Q000453:epidemiology* / Q000235:genetics; D004485:Eczema / Q000453:epidemiology / Q000235:genetics*; D005260:Female; D005838:Genotype; D006801:Humans; D057182:Mendelian Randomization Analysis; D011110:Polymorphism, Genetic; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects / Q000235:genetics*; D006255:Rhinitis, Allergic, Seasonal / Q000453:epidemiology / Q000235:genetics; D012306:Risk; D012959:Socioeconomic Factors; D006113:United Kingdom; D044465:White People / Q000235:genetics; D055815:Young Adult
chemical_list: C489332:ADH1B protein, human; D000426:Alcohol Dehydrogenase
keywords: ADH; ADH1B; ALSPAC; Alcohol; Alcohol dehydrogenase; Avon Longitudinal Study of Parents and Children (ALSPAC); GWAS; Genome Wide Association Study; Mendelian randomization; PCA; Principal Components Analysis; asthma; atopy; birth cohort; pregnancy; prenatal exposure